Abnormal Liver Tests

General Overview

• Hepatocellular pattern
  • Disproportionate elevation of AST and ALT compared with alkaline phosphatase
  • AST : ALT >2 (with elevated GGT), consider Alcohol
• Cholestatic pattern
  • Disproportionate elevation in alkaline phosphatase compared with AST and ALT
    • Painful (stone/infection) vs. painless (tumour)
• Mixed pattern
• Isolated hyperbilirubinemia (with normal serum AST/ALT/ALP)

R ratio

• R=(𝐴𝐿𝑇 ÷ 𝐴𝐿𝑇 𝑈𝐿𝑁)/(𝐴𝐿𝐾 ÷𝐴𝐿𝐾 𝑈𝐿𝑁)
  • R > 4 Hepatocellular injury
  • R < 2 Cholestatic injury
  • R 2-5 Mixed pattern
  • Note: All of these patterns may have elevated bilirubin

Causes of elevated AST/ALT

• Hepatic
  • Alcoholic liver disease <8xULN
  • NAFLD (steatosis, NASH) <4xULN
  • Ischemic hepatitis >50xULN
  • Acute viral hepatitis >20xULN
  • Chronic viral hepatitis
  • Hemochromatosis
  • Wilson’s Disease
  • Alpha 1 antitrypsin deficiency
  • Liver trauma
  • HELLP syndrome
  • Drug-induced liver injury
  • Autoimmune hepatitis
• Non-hepatic
  • Skeletal muscle damage/ rhabdomyolysis
  • Cardiac muscle damage
  • Thyroid disease
  • Strenuous exercise
  • Hemolysis
  • Adrenal insufficiency
  • Celiac disease
  • Malignant infiltration (breast cancer, small cell lung cancer, lymphoma, melanoma, myeloma)

Management of elevated AST/ALT

• History, Physical
  • Risk of fatty liver, viral hepatitis
  • Signs of liver failure
• Discontinue hepatotoxic medications and alcohol
• Find underlying cause:

1. CBC/platelet, AST/ALT, Alk Phos, Total Bili, Albumin, PT/INR
2. HBsAg, HBcAb, HBsAb, HCV Ab (with PCR if positive), iron panel, abdominal ultrasound r/o fatty liver
   • If mild elevation and history of alcohol consumption, can repeat initial testing after 3-6 months before moving on to additional testing
3. Autoimmune: ANA, ASMA, Anti-LKM, IgG
4. Ceruloplasmin (Wilson), Anti-TTG (with total IgA), TSH, alpha-1 antitrypsin level (phenotyping if indicated)
5. May consider muscle disorder (CK or aldolase), tick-borne, adrenal insufficiency
6. Refer to hepatologist for liver biopsy
   • If mild elevation may consider expectant management rather than referral
   • Refer immediately of acute liver failure for possible transplant

• If severe elevation, add
  • bhCG (r/o HELLP)
  • HAV IgM Ab, Hep C Viral RNA,
  • HSV Ab, VZV Ab, EBV, CMV Ag,
  • Serum drug panel (consider n-acetyl cysteine for tylenol), urine toxicology
  • Abdominal Doppler US (r/o vascular obstruction/Budd-Chiari syndrome)

Hyperbilirubinemia

• Jaundice usually hyperbilirubinemia
  • If normal bilirubin, consider carotenemia

see Jaundice in pediatrics

Causes of elevated bilirubin

• Unconjugated hyperbilirubinemia
  • Overproduction (hemolysis)
    • Hypersplenism
    • G6PD, Thalassemia, Sickle cell, spherocytosis, elliptocytosis, malaria
    • Drug-induced/auto-immune
  • Impaired hepatic uptake
    • Portosystemic shunt
    • Drugs (Rifampin)
  • Impaired conjugation
    • Hyperthyroidism, hepatitis, Wilson's
    • Gilbert or Crigler-Najar (LFT normal, no evidence of hemolysis/sepsis)
      • History of jaundice during stress/fasting
  • Stressor (sepsis) may act on all the above
• Conjugated hyperbilirubinemia
  • Elevated ALP/GGT
    • Biliary obstruction (eg, gallstones, tumor)
  • Elevated ALT/AST
    • Liver disease causing hepatocellular dysfunction (eg, hepatitis, sepsis, or hepatotoxic drugs)
  • Normal ALP/GGT
    • Inherited disorders (eg, Dubin Johnson or Rotor syndrome)

Investigations

• CBC
• LFT
• INR, albumin
• Hemolytic work-up
  • Reticulocytes
  • Haptoglobin
  • LDH
  • Smear
  • Coomb's
• Family History consider G6PD screen